Pharmacologic enhancement of adaptive growth after extensive small-bowel resection

Adaptive hyperplasia, especially of the ileum, is a well-known and extensively studied physiological response that is responsible for the ability of animals to survive extensive small-bowel resection. Luminal nutrients, endogeneous secretions, and humoral factors are considered to be important mediators of this compensatory increase in absorptive surface area. Recently, prostaglandins have been shown to exert a trophic influence on the intestine. The object of this study was to determine whether it is possible to enhance the resection-induced intestinal hyperplasia with a new prostaglandin E₂ (PGE₂) analog (Ro 22–1327). In four groups of rats 4–5 weeks of age, a 70%–80% midintestinal resection was performed. One group (A1) was treated with Ro 22–1327 for 14 days by daily oral gavage; another was treated for 4 weeks (B1). The remaining two groups were used as controls and treated with placebo for 14 days (A2) and 4 weeks (B2). A fifth group was subjected to sham laparotomy without intestinal resection and treatment. In both groups treated for 14 days, relaparotomy was performed on the 14th day and intestinal length and width were measured. Threafter, treatment was discontinued for another 14 days. After 4 weeks the intestinal segments from all animals were removed (jejunal and ileal remnants, cecum, and colon). Lenght, width, and wet and dry weights were measured and surface areas were calculated. The results demonstrate a significant increase in all intestinal parameters in groups treated with the PGE₂ analog. In the small intestine, the trophic response was expressed more in the jejunum. Postresectional adaptive growth in the cecum and colon was also enhanced by Ro 22–1327. The results of this study suggest that trophic substances could be used therapeutically to increase intestinal surface area in patients with short bowel syndrome.Offprint requests to: M. E. HöllwarthSupported by funds from the National Heart Lung and Blood Institute (HL 26441) and Hoffmann-La Roche Inc.